1. Field of the Invention
The present invention relates to improvements and applications with respect to the teachings of the above referenced patent applications in the general area of mass spectrometry as shown in FIG. 1 including ion mobility spectrometry (IMS) where the vacuum is absent.
2. Background Art
Accurate mass (AM) measurements have been widely utilized for a variety of applications including determination of metabolites, identification of peptides for database searching, and confirmation of pharmaceuticals and their impurity and degradation products. The attractiveness of the AM technique is its capability of determining elemental composition of an unknown molecule with the mass accuracy at low or below ppm level. As a result, AM measurements alone can often provide the definite structure of the molecule so that usually required tandem mass spectrometry (MS/MS) analysis for structural elucidation is no longer necessary. In addition, when applied to MS/MS, AM analyses of precursor and product ions are always valuable confirmation for structural elucidation of molecules of interest. While the technique has generated very impressive results and has become increasingly popular, the majority of the mass spectrometry community cannot afford access to the instruments with AM capability such as Fourier Transform mass spectrometer (FTMS), double focusing sector instrument, tandem time of flight (TOF/TOF), and quadrupole time of flight (qTOF).
Fortunately, the novel mass spectrometry data processing technology described in the cross-referenced patent applications makes it possible to perform AM analysis on a low resolution mass spectrometer and to improve mass accuracy on a high resolution mass spectrometer. Specifically, the details on this technology are described in U.S. patent application Ser. No. 10/689,313. Briefly, the technology achieves high mass accuracy by unique mass spectrometry calibration procedures including instrument (external) and an internal calibration. The external calibration employs sophisticated mathematics and statistics to calculate exact mass location and isotopic distribution, to determine instrument peak shape functions, and to derive calibration filters from a set of calibration ions, while an internal calibration is used to compensate for instrument drifting in real time or near real time analysis.
The present invention describes the development of mass spectral calibration involving overlapped isotope clusters, tandem MS, and higher resolution scan modes on typically a lower resolution mass spectrometer.